PLoS Genetics最新文献

{"title":"Matrix Metalloprotease 1 (Mmp1) promotes cell fate change for epithelial-to-epithelial transition during regeneration after radiation damage in Drosophila.","authors":"Michael Shiferaw, Lauren Orr, Korneel Hens, Tin Tin Su","doi":"10.1371/journal.pgen.1012257","DOIUrl":"10.1371/journal.pgen.1012257","url":null,"abstract":"<p><p>Ionizing radiation (IR) is used to treat cancer, but therapeutic failure occurs when surviving cancer cells change fate and regenerate tumors through acquired stem cell-like properties. While transcriptional mechanisms underlying cell fate plasticity have been characterized, the cellular processes enabling cell movement during tissue regeneration remain unclear. We reported previously that hinge cells of the Drosophila larval wing disc convert to pouch fate and translocate to help regenerate the pouch that suffers from more IR-induced apoptosis. We report here that IR increases the expression of extracellular proteins in the hinge, including secreted proteases and cell adhesion modulators. Functional validation using RNA interference revealed that secreted Matrix Metalloprotease 1 (Mmp1) and the related secreted protease homolog Scarface (Scaf) are required in hinge cells for IR-induced cell fate conversion and translocation. IR, we found, induces Mmp1 and scaf transcripts in hinge cells via cell-autonomous JNK signaling. Overexpression of Mmp1 specifically in the hinge was sufficient to elevate Mmp1 protein levels throughout the disc and induced cell fate change of both hinge and non-hinge cells but only in the context of irradiation. Confocal imaging in a time course demonstrated that cells undergoing fate conversion remain within the epithelial layer with little evidence for delamination or epithelial-mesenchymal transition (EMT). We propose that remodeling of the extracellular environment is a critical mechanism that enables cellular reorganization during tissue regeneration. Mmp enzymes are important for cancer biology because of their role in ECM remodeling, extracellular signaling, and EMT. Our findings demonstrate for the first time that Mmp1 is necessary and sufficient for one epithelial cell type to switch to another epithelial cell type after radiation damage. These results provide a mechanistic basis for radiation therapy-induced cell fate plasticity.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012257"},"PeriodicalIF":3.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Complexin in ivermectin resistance in body lice.","authors":"","doi":"10.1371/journal.pgen.1012258","DOIUrl":"10.1371/journal.pgen.1012258","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1007569.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012258"},"PeriodicalIF":3.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent evolution of cryptic triploids in cultivated enset increases yield.","authors":"Yann Dussert, James S Borrell, Jonathan Stocks, Harriet V Hunt, Oliver W White, Paul Wilkin, Richard Buggs, Lucie Büchi, Sebsebe Demissew, Feleke Woldeyes, Ilia J Leitch, Wendawek M Abebe, Richard A Nichols","doi":"10.1371/journal.pgen.1012241","DOIUrl":"10.1371/journal.pgen.1012241","url":null,"abstract":"<p><p>The high incidence of polyploidy in crops could be explained if domestication involved the selection of polyploids (cytotypes with more than two sets of chromosomes). Ancestral horticulture could have targeted desirable traits including yield, robustness to stress or disease, rather than requiring knowledge of polyploidy itself. We find evidence for this process underway in enset (Ensete ventricosum, Musaceae), a highly resilient crop constituting the main staple for over 20 million people in Ethiopia, which is clonally propagated and cultivated for its starch-rich corm and pseudostem. Prior to this study, enset was thought to be exclusively diploid (2n = 2x = 18). Using a newly-assembled chromosome-scale reference genome and sequence data from 723 wild and domesticated enset individuals from southwestern Ethiopia, we demonstrate that around 20% of cultivated enset clones are triploid. We show that triploidy has arisen multiple times independently, that the triploid lineages have been given distinct landrace names, and planted disproportionately frequently. Enset triploid clones also have a higher pseudostem volume than diploids on average. As well as providing evidence for enduring selection on triploids, our results reveal valuable genetic diversity captured by these triploid lines. They represent key resources for scientifically directed breeding of this major crop in the Ethiopian agrosystem, and could improve food security in Sub-Saharan Africa.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012241"},"PeriodicalIF":3.9,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans.","authors":"Bryan A Martinez, Anne M Stene, Jonathan I Hauser, Karla J Opperman, Jonathan N Sachs, Anthony R Braun, Matthew S Gill","doi":"10.1371/journal.pgen.1012240","DOIUrl":"10.1371/journal.pgen.1012240","url":null,"abstract":"<p><p>Insulin / insulin-like growth factor signaling (IIS) in C. elegans is mediated by the DAF-2 receptor and insulin-like peptides (ILP) that can act as agonists or antagonists. DAF-2 signaling is also affected by DAF-2B, a truncated, non-signaling, secreted isoform of DAF-2 that acts as a decoy receptor by sequestering ILPs. In this study, we performed a forward genetic screen for modifiers of DAF-2B protein expression and identified a mutation in unc-31 that increased DAF-2B. UNC-31 is involved in dense core vesicle docking and is required for neuropeptide secretion, including ILPs. As a result, unc-31 mutants constitutively enter the dauer larval stage and are long-lived due to reduced IIS. We find that increased nervous system DAF-2B accumulation is associated with reduced agonist ILP availability, in both unc-31 mutants and wild type worms. Using auxin-induced degradation (AID) and fluorescence lifetime imaging microscopy-Förster resonance energy transfer (FLIM-FRET), we find that a significant fraction of nervous system DAF-2B is in the form of a heterodimeric complex with a full-length DAF-2 receptor isoform, representing a new class of DAF-2 hybrid receptor. In unc-31 mutants, DAF-2B also undergoes endocytosis in neurons in an AP2-dependent manner and genetic manipulation of daf-2b in the unc-31 mutant suggests that DAF-2B homodimers may function to reinforce a reduced insulin signaling state by clearing agonist ILPs from the extracellular space. These findings indicate that DAF-2B not only forms homodimers, but also hybrid receptors with full-length DAF-2, to regulate the activity of the large and diverse family of ILPs in C. elegans.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012240"},"PeriodicalIF":3.9,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoperiodic patterns in miRNA-mRNA pairs and tRNA fragments revealed by time-course co-sequencing in Arabidopsis.","authors":"Chun Chung Leung, Daniel A Tarté, Joshua M Gendron","doi":"10.1371/journal.pgen.1012229","DOIUrl":"10.1371/journal.pgen.1012229","url":null,"abstract":"<p><p>In plants, the response to photoperiod is marked by global reprogramming of gene expression that drives extensive developmental changes. Small RNAs (sRNAs) play important roles in this process, but a comprehensive characterization of micro RNAs (miRNAs) and the more recently recognized transfer RNA fragments (tRFs) within this context is lacking. Herein, we characterize the patterns of miRNAs and tRFs in Arabidopsis by performing time-course sRNA-sequencing across three photoperiods. By comparing with our previous messenger RNA (mRNA) sequencing time-courses, we identified positively- or inversely-correlated miRNA-mRNA pairs between the two co-sequenced datasets that suggest photoperiodic sRNA regulations. Furthermore, we revealed 20 patterns of photoperiodic tRFs. These patterns are linked to the transfer RNA (tRNA) isotypes and positions they derive from, suggesting that tRFs are subjected to photoperiodic regulation. Finally, we present a major update to our web-app \"Photo-Graph,\" (http://gendron-lab.shinyapps.io/PhotoGraph) featuring new visualizations of this mRNA-sRNA co-sequencing dataset. In summary, our findings indicate that plants regulate sRNAs within a diel cycle in a photoperiodic manner and form highly-correlated pairs with mRNAs.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012229"},"PeriodicalIF":3.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-ancestry colocalization approaches.","authors":"Cathy Shen, Josée Dupuis, Qihuang Zhang","doi":"10.1371/journal.pgen.1012221","DOIUrl":"10.1371/journal.pgen.1012221","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but many are non-causal. Statistical fine-mapping methods aim to pinpoint the most likely causal variants among the many associated ones. While most fine-mapping methods were originally limited to single ancestry analysis, multi-ancestry fine-mapping methods are now available, leveraging differences in linkage disequilibrium (LD) and minor allele frequencies (MAFs) across ancestries to improve fine-mapping resolution. However, the biological relevance of the putative causal variants identified through fine-mapping often remains unclear. Colocalization methods improve interpretability by integrating GWAS data with other functional genomics datasets to assess whether two traits share the same causal variants. Despite the growing availability of multi-ancestry data, there are currently no established methods for multi-ancestry colocalization. In this study, we propose multi-ancestry colocalization approaches through the integration of multi-ancestry fine-mapping methods, SuSiEx and MsCAVIAR, with single ancestry colocalization methods, coloc and eCAVIAR. We introduce coloc_SuSiEx, eCAVIAR_SuSiEx, eMsCAVIAR and coloc_MsCAVIAR. The performance of the proposed approaches is evaluated and compared through simulation studies. In loci with a single causal variant, credible set sizes across the four approaches were comparable, as was the prioritization of the true causal variant. MsCAVIAR-based approaches were more computationally expensive compared to SuSiEx-based approaches, which is an important consideration for the analysis of regions with multiple causal variants. Compared to the coloc-based approaches, the eCAVIAR-based approaches tended to report lower loci level colocalization posterior probabilities. For the analysis of loci with multiple causal variants, coloc_SuSiEx is the preferred approach. We apply the proposed approaches to perform a colocalization analysis of multi-ancestry T2D GWAS data from the DIAMANTE Consortium and European pQTL data from the INTERVAL study. This work addresses the increasing need for multi-ancestry approaches to colocalization analysis as more multi-ancestry data become available.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012221"},"PeriodicalIF":3.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-family and phage-specific gene requirements for Klebsiella infection revealed by scalable RB-TnSeq genetic screens.","authors":"Marissa R Gittrich, Courtney M Sanderson, Cara M Noel, Erica Babusci, Sumeyra C Selbes, Madeline Svab, Isabella Murray, Collis Bousliman, Ami Fofana, Aghiad Daboul, Jonathan Leopold, Alessandra Gonçalves de Melo, Marion Urvoy, Sylvain Moineau, Vivek K Mutalik, Matthew B Sullivan","doi":"10.1371/journal.pgen.1012233","DOIUrl":"10.1371/journal.pgen.1012233","url":null,"abstract":"<p><p>Bacteriophages are being cataloged at an accelerating pace and are recognized as key players in nutrient and energy cycling across ecosystems. Yet the bacterial genetic determinants that govern phage-host specificity and infection success remain poorly understood, particularly in clinically and ecologically important genera such as Klebsiella where prior receptor characterization has been almost entirely limited to capsulated strains. Here we used a randomly barcoded, genome-wide, loss-of-function transposon mutant library (RB-TnSeq) of Klebsiella sp. M5al, a naturally acapsular, nitrogen-fixing rhizobacterium, to generate the first systematic, cross-family map of phage receptor gene dependencies in Klebsiella. Challenging the library against 25 double-stranded DNA phages spanning five families in 213 parallel assays, we identified 42 bacterial genes associated with phage infection, of which 15 had no prior association with phage infection in any bacterial system. Disruption of surface receptor biosynthesis genes conferred cross-resistance across multiple phage families, while intracellular gene disruptions had predominantly phage-specific effects. Clonal validation of eight genes confirmed LPS outer core biosynthesis genes as primary receptor determinants alongside additional host factors spanning outer membrane transport, cofactor biosynthesis, and two-component signaling. Comparative analysis across all 25 phages revealed that phage genus rather than family is the stronger predictor of host gene dependency profiles, a finding with direct implications for the functional annotation of uncharacterized phage isolates and rational phage cocktail design. Together, these findings provide a community resource for linking phage genomic diversity to functional host interaction space in this ecologically and clinically important genus.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012233"},"PeriodicalIF":3.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tumor-suppressive role of the PRC1 Polycomb epigenetic complex in the maintenance of adult Drosophila intestinal stem cell identity.","authors":"Aurélia Joly, Ana-Maria Popmihaylova, Corinne Rancurel, Julie Soltys, Rihab Loudhaief, Armel Gallet, Edan Foley, Anne-Marie Martinez, Raphaël Rousset","doi":"10.1371/journal.pgen.1012226","DOIUrl":"10.1371/journal.pgen.1012226","url":null,"abstract":"<p><p>Chromatin modulators, like Polycomb group proteins, are key epigenetic regulators of gene expression and are frequently mutated in cancers. In adult stem cells, epigenetic regulation maintains their identity and controls their differentiation during homeostasis or aging, but its direct role in tumorigenesis remains unclear. Here we developed a novel tumor model in Drosophila by exploring the function of Polycomb Repressive Complex 1 (PRC1) in adult intestinal stem cells (ISCs). Disrupting core PRC1 components in ISCs induces the formation of small cell clusters devoid of intestinal markers, a novel phenotype linked to premature mortality under stress. These clusters exhibit neoplastic characteristics such as overproliferation and continuous growth in serial transplantations, leading to their designation as tumor-initiating intestinal cells (TIICs). While JAK/STAT signaling contributes to TIIC growth, the NF-κB-related Toll/Imd immune pathways restrict their expansion independently of cell death. Altogether, our results highlight PRC1 as an epigenetic tumor suppressor in adult stem cells.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012226"},"PeriodicalIF":3.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells.","authors":"Giovanna Weykopf, Wendy A Bickmore, Simon C Biddie, Elias T Friman","doi":"10.1371/journal.pgen.1012222","DOIUrl":"10.1371/journal.pgen.1012222","url":null,"abstract":"<p><p>Common genetic variants contribute to risk for complex human diseases. However, despite thousands of associations, variants modulating disease risk and their functional impact remain largely unknown. This includes SARS-CoV-2 infection, where outcomes range from asymptomatic to fatal. Most genetic risk variants associated with COVID-19 disease, identified through genome wide association studies, are located in the non-coding genome and may function by altering gene expression in disease-relevant cells and tissues. To address this at scale, we tested >4800 severe COVID-19-associated variants to determine the impact of individual variants and variant combinations on regulatory activity using Self-Transcribing Active Regulatory Region sequencing, a massively-parallel reporter assay. Focusing on variants that may have their impact in the lung, in a lung epithelial cell line (A549) we identify 166 variants within active sequences, of which 29 modulate activity allele-specifically. Evaluating variant combinations, we observe both additive and non-additive effects on regulatory activity. We employ state-of-the-art deep learning models to interpret allele-specific variant effects on regulatory activity and endogenous genomic features. Our work provides a set of prioritised severe COVID-19-associated variants that modulate regulatory activity in lung epithelial cells, candidate transcription factors, and candidate target genes with potential to be disease modifying.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012222"},"PeriodicalIF":3.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting evolutionary patterns of helper and sensor NRC NLRs in lettuce reflect functional divergence following subfunctionalization.","authors":"Hsuan Pai, Toshiyuki Sakai, Andres Posbeyikian, Raoul Frijters, Yu Sugihara, Mauricio P Contreras, Jiorgos Kourelis, Hiroaki Adachi, Sophien Kamoun, AmirAli Toghani","doi":"10.1371/journal.pgen.1012245","DOIUrl":"10.1371/journal.pgen.1012245","url":null,"abstract":"<p><p>Nucleotide-binding domain and leucine-rich repeat immune receptors (NLRs) are known for their rapid evolution, even at the intraspecific level, yet the rates of evolution differ significantly across NLRs. However, the degree to which evolutionary patterns reflect functional divergence remains poorly understood, notably in important crop species. Within the NRC (NLR Required for Cell Death) network in Asterids, sensor NLRs detect pathogen presence but require NRC helpers for signaling and to confer immunity. We conducted a comparative analysis of NLRs across 40 Solanales and 29 Asterales genomes to explore NRC network expansion and diversification within the less-studied Asterales order. Our findings reveal that the NRC network has expanded less in Asterales compared to Solanales. We functionally validated an Asterales NRC network with 2 helpers and 9 sensors in common lettuce (Lactuca sativa). Through selection analysis and structural modeling of NRC gene family in the Lactuca genus, we found distinct evolutionary trajectories between NRC helpers and sensors. Sensors reliant on the phylogenetically conserved helper NRC0 experience limited diversification, whereas sensors dependent on other NRC helpers show higher rates of positive selection and gene duplication. Our results highlight the lineage- and function-specific evolution of the NRC network, offering insights into the evolutionary pressures shaping plant immune receptor networks.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 7","pages":"e1012245"},"PeriodicalIF":3.9,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}